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Abstract Human capital and social capital are crucial in shaping entrepreneurial decisions, yet their combined effects on entrepreneurship entry remain insufficiently explored. This study uses data from the China Household Tracking Survey (2010–2018) to examine how the coupling of human and social capital influences entrepreneurship entry. By defining human-social capital coupling as the interdependence between these two forms of capital, we estimated its nonlinear impact using generalized propensity score matching and analyzed variations across gender and region. The results revealed that human capital-social capital coupling mediated the relationship between these capitals and entrepreneurship entry, following a significant N-shaped trend with identified thresholds. The impact of this coupling was also influenced by gender and regional variations. The study contributes to the literature by introducing a novel perspective on capital coupling, assessing its threshold effects, and highlighting gender and regional disparities. Individuals should understand and use the human capital-social capital coupling to guide their actions; policymakers are encouraged to consider and enhance the coupling between human and social capital in their entrepreneurship support strategies.

Abstract Whether and how the non-lesional sensorimotor cortex is activated and contributes to post-injury motor recovery is controversial. Here, we investigated the role of interhemispheric pathway from the contralesional to ipsilesional premotor cortex in activating the ipsilesional sensorimotor cortex and promoting recovery after lesioning the lateral corticospinal tract at the cervical cord, by unidirectional chemogenetic blockade in macaques. The blockade impaired dexterous hand movements during the early recovery stage. Electrocorticographical recording showed that the low frequency band activity of the ipsilesional premotor cortex around movement onset was decreased by the blockade during the early recovery stage, while it was increased by blockade during the intact state and late recovery stage. These results demonstrate that action of the interhemispheric pathway changed from inhibition to facilitation, to involve the ipsilesional sensorimotor cortex in hand movements during the early recovery stage. The present study offers insights into the stage-dependent role of the interhemispheric pathway and a therapeutic target in the early recovery stage after lesioning of the corticospinal tract.

ObjectiveTo determine whether outer membrane vesicles (OMVs) of the periodontal pathogen Porphyromonas gingivalis (P. gingivalis) can infect gingival keratinocytes and stimulate reactive oxygen species (ROS) production, and to assess whether stannous fluoride (SnF2), stannous chloride (SnCl2) or 0.454% SnF2 toothpaste diluents can inhibit OMV infection.MethodsOMVs were isolated from P. gingivalis culture and their morphology was characterized using scanning electron microscopy and transmission electron microscopy. OMVs were harvested, separated from parent bacteria, labeled with fluorescent probes, and added to proliferating gingival keratinocytes. Infection was monitored by measuring uptake of fluorescence. Free radicals and ROS were quantified by adding a separate CellROX fluorescent probe following 24 h incubation with OMVs, and automated fluorescence imaging was used to assess ROS generation rates. A dose response range of SnF2 and SnCl2 concentrations as well as 0.454% SnF2 toothpaste dilutions were added to OMVs to examine their potential to neutralize OMV infectivity and protect gingival keratinocytes from development of oxidative stress. The mechanism of SnF2 inhibition of OMV infection was studied by binding SnF2 with purified lipopolysaccharides (LPS) from the bacterial culture and examining the binding of stannous to LPS using mass spectrometry.ResultsLarge numbers of OMVs were formed in P. gingivalis culture medium. They were purified along with isolating soluble LPS. Fluorescence imaging revealed that OMVs infected gingival keratinocytes and promoted oxidative stress in a dose-dependent manner. SnF2, SnCl2, and SnF2 toothpaste inhibited OMV infectivity (p

Background: The causal relationship between chronic venous insufficiency (CVI) and cardiovascular diseases (CVDs) has yet to be elucidated. Herein, we implement Mendelian randomization (MR) analysis to investigate the causal association. Methods: A two-sample MR approach using genetic data from FinnGen and genome-wide association studies (GWAS) Catalog was applied to investigate the causal relationship between CVI and CVDs. This study assessed 77 single nucleotide polymorphisms (SNPs) as instrumental variables, employing random-effect inverse-variance-weighted MR, weighted median, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and Robust Adjusted Profile Score (RAPS) methods. Multivariable MR (MVMR) considered confounding factors. Results: Genetically predicted CVI was associated with reduced heart failure risk (odds ratio (OR) = 0.96, 95% confidence interval (95% CI): 0.93–0.99, p = 0.025) and increased atrial fibrillation risk (OR = 1.06, 95% CI: 1.03–1.09, p = 0.0002). MVMR, adjusting for venous thromboembolism (VTE), lower limb ulceration, obesity, smoking, and alcohol, attenuated these associations. No significant links were found with hypertension, aortic aneurysm, coronary artery disease, myocardial infarction, valvular heart disease, or stroke. Conclusions: This MR study supports an association between CVI and CVDs, which may imply CVI should be monitored during the treatment of heart failure and atrial fibrillation.

In this study, tobermorite was prepared by hydrothermal method using two kinds of typical solid waste as raw materials, i.e., fly ash aluminum extraction slag (by-product in the process of fly ash hydrochloric acid aluminum extraction) and papermaking white mud. The XRD, SEM, FTIR, TG-DSC and Specific surface area and porosity were used to investigate the influence of Ca/Si ratio, alkalinity, hydrothermal conditions and other factors on the synthesis products, and the formation mechanism of tobermorite. The adsorption capacity of tobermorite was investigated by adsorption experiments. The effects of different dosage, initial concentration of Cd2+ and adsorption time on the adsorption behavior were investigated to understand the adsorption mechanism of tobermorite on Cd2+. The results show that the well crystal tobermorite can be synthesized at 180 °C for 6 h with the Ca∶Si molar ratio of 0.8 and the NaOH addition amount of 2.5%−5.0%. The specific surface area of tobermorite is 80.956 m2/g, the total pore volume is 0.218 cm3/g, the pore size is 1.21 nm, and the crystallization of tobermorite is 97%. The microstructure of tobermorite is dominated by short fibers and has a good thermal stability below 650 °C. The formation process of tobermorite can be described that the CaO in papermaking white clay is converted into Ca(OH)2 and the amorphous silicon dioxide is transformed into sodium silicate. The gel blocks material is formed by calcium hydroxide and sodium silicate solution. Tobermorite whiskers are formed, and the whiskers gradually exfoliate, split and grow to form tobermorite fibrous materials. The Cd2+ removal rate of tobermorite can reach 99.99% at pH value of 3, the dosage of tobermorite is 2.5 g/L, and the concentration of Cd2+ is 100 mg/L. The adsorption of Cd2+ by modified tobermorite fits the quasi-second-order kinetic equation and the Langmuir model, and is controlled by membrane diffusion and intra-particle diffusion, and the chemisorption is the main control step. The study indicates that tobermorite can be prepared from aluminum extraction slag with fly ash and white paper mud. The tobermorite prepared had a good adsorption effect on heavy metals and can be used as a high efficient adsorbent for heavy metal ions. Also, the study realizes the collaborative utilization of two typical solid waste resources in different industries, and provides a potential method for the treatment of wastewater containing Cd2+ and other heavy metal ions.

Recent studies show that the shape of the internal cavity with periodic distribution has a significant impact on the characteristics of the anechoic coating. In this study, we proposed a genetic algorithm-based method for optimizing the design parameters of anechoic coating. By transforming the 3D finite element model (FEM) of the anechoic coating to a 2D axisymmetric finite element model (AFEM), and COMSOL with MATLAB co-simulation combined with the genetic algorithm applied to obtain the optimal parameters. Lots of simulation results demonstrate that as the number of generated segments on the rotating surface in the internal cavity increases, the sound absorption performance of the anechoic coating greatly improves. The expected optimization effect is achieved by substituting the optimized parameters into 3D FEM. Moreover, the reflection coefficient of an anechoic coating gradually increases with the increasing of incident angles. In the middle-high frequency range, when synthetical optimizing the material properties and cavity shape, better sound absorption performance can be obtained in comparison to the case where only the cavity shape is optimized.

The content of Cu2+ in lubricants is an essential indicator for determining the quality of the lubricant and predicting mechanical failure. Finding an effective and sensitive method for detecting Cu2+ in lubricants is of great importance in oil monitoring. In this work, AgInS2 (AIS) and AgInS2-ZnS (ZAIS) nanoparticles (NPs) were synthesized by a simple one-step approach via in-situ surface modification by oleylamine. The as-synthesized AIS and ZAIS NPs exhibit good dispersion stability in various apolar media. The photoluminescence (PL) of AIS and ZAIS NPs as lubricating additives could reflect and monitor the lubrication state of steel-copper pairs due to the quenching effect of Cu2+ from the friction process. With an optimum concentration of 0.5 wt% in paraffin oil, the friction coefficient of the AIS and ZAIS NPs at 100 N was decreased by 56.8 and 52.1% for steel-steel contacts, respectively. ZAIS was observed to be more effective than AIS in improving anti-wear (AW) and extreme pressure (EP) properties, with a load-bearing capacity of up to 1100 N. Characterization of the wear tracks by SEM and XPS indicates that a tribofilm composed of metal sulfides and oxides was formed during the lubricating process. This work not only reveals AIS and ZAIS NPs as a new class of promising candidates for lubricating additives but also unveils their potential for monitoring lubricant conditions and exploring lubricant service life.

Cyfluthrin, a typical type II pyrethroid pesticide, is widely used in house hygiene and agricultural pest control. Several epidemiological investigations have found that maternal pyrethroid exposure is connected to adverse pregnancy outcomes. However, the underlying mechanisms remain to be elucidated. Thus, we evaluated the effect of cyfluthrin exposure during pregnancy on placenta development in vivo. In the current study, Pregnant SD rats were randomly divided into four groups and administered 6.25, 12.5, and 25 mg/kg body weight cyfluthrin or an equivalent volume of corn oil by gavage from GD0 to GD19. The results have shown that gestational exposure to cyfluthrin exerted no effect on the fetal birth defect, survival to PND4, or fetal resorption and death. However, live fetuses and implantation sites significantly decreased in the high-dose cyfluthrin-treated group. Moreover, a significant reduction in placenta weight and diameter was observed in rats. Correspondingly, the fetal weight and crown-rump length from dams exposed to cyfluthrin were reduced. Cyfluthrin-treat groups, the total area of the placenta, spongiotrophoblast area, and labyrinth area had abnormal changes. Meanwhile, the area of blood sinusoid and CD34-positive blood vessel numbers in the placenta were considerably reduced, as well as abnormal expression of placental pro-angiogenic and anti-angiogenic factors in dams exposed to cyfluthrin. Further observation by transmission electron microscopy revealed significant changes in the ultrastructure of the medium-dose and high-dose groups. Additional experiments showed gestational exposure to cyfluthrin inhibited proliferation and induced apoptosis of placentas, as decreased PCNA-positive cells and increased TUNEL-positive cells. Furthermore, western blot and qPCR analysis revealed that gestational exposure to medium-dose and high-dose cyfluthrin increased the expression of GRP78, and three downstream mRNA and proteins (p-eIF2α, ATF4, and CHOP) of the PERK signaling, indicating that endoplasmic reticulum (ER) stress-mediated PERK/eIF2α/ATF4/CHOP signaling pathway in rat placentas was activated. Our study demonstrated that gestational exposure to cyfluthrin leads to placental developmental disorder, which might be associated with ER stress-mediated PERK signaling pathway.

A growing number of human diseases have been found to be associated with aberrant DNA methylation, including cancer. Mutations targeting genes encoding DNA methyltransferase (DNMT), TET family of DNA demethylases, and isocitrate dehydrogenase (IDH1, IDH2) that produce TET inhibitory metabolite, 2-hyoxyglutarate (2-HG), are found in more than half of acute myeloid leukemia (AML). To gain new insights into the regulation of DNA de/methylation and consequence of its alteration in cancer development, we searched for genes which are mutated in a manner that is linked with gene mutations involved in DNA de/methylation in multiple cancer types. We found that recurrent CBFB-MYH11 fusions, which result in the expression of fusion protein comprising core-binding factor β (CBFB) and myosin heavy chain 11 (MYH11) and are found in 6∼8% of AML patients, occur mutually exclusively with DNMT3A mutations. Tumors bearing CBFB-MYH11 fusion show DNA hypomethylation patterns similar to those with loss-of-function mutation of DNMT3A. Expression of CBFB-MYH11 fusion or inhibition of DNMT3A similarly impairs the methylation and expression of target genes of Runt related transcription factor 1 (RUNX1), a functional partner of CBFB. We demonstrate that RUNX1 directly interacts with DNMT3A and that CBFB-MYH11 fusion protein sequesters RUNX1 in the cytoplasm, thereby preventing RUNX1 from interacting with and recruiting DNMT3A to its target genes. Our results identify a novel regulation of DNA methylation and provide a molecular basis how CBFB-MYH11 fusion contributes to leukemogenesis.

Background: The great saphenous vein (GSV) is the most commonly used conduit for coronary arterial bypass graft. However, the status of the GSV, including metabolic dysfunction such as diabetes mellitus (DM) complication, is strongly associated with vein graft failure (VGF). To date, the molecular mechanism underlying VGF remains elusive. Detailed characterization of the cellular components and corresponding expression regulation in GSVs would be of great importance for clinical decision making to reduce VGF. Methods: To this end, we performed single-cell RNA sequencing to delineate cellular heterogeneity in three human GSV samples. Results: Scrutinization of cellular composition and expression revealed cell diversity in human GSVs, particularly endothelial cells (ECs). Our results unraveled that functional adaptation drove great expression differences between venous ECs and valvular ECs. For instance, cell surface receptor ACKR1 demarcated venous Ecs, whereas ACRK3/ACKR4 were exclusively expressed by valvular ECs. Differential gene expression analysis suggested that genes highly expressed in venous ECs were mainly involved in vasculature development and regulation of leukocyte adhesion, whereas valvular ECs have more pronounced expression of genes participating in extracellular matrix organization, ossification and platelet degranulation. Of note, pseudo-time trajectory analysis provided in silico evidence indicating that venous ECs, valvular ECs and lymphatic vessels were developmentally connected. Further, valvular ECs might be an importance source for lymphatic vessel differentiation in adults. Additionally, we found a venous EC subset highly expressing IL6, which might be associated with undesirable prognosis. Meanwhile, we identified a population of ANGPTL7+ fibroblasts (FBs), which may be profibrotic and involved in insulin resistance in human GSVs. Additionally, our data suggest that immune cells only accounted for a small fraction, most of which were macrophages. By assessing the intertwined remodeling in metabolic dysfunction that potentially increases the gene expression regulatory network in mural cells and leukocytes, we found that transcription factor KLF9 likely operated a proinflammatory program, inducing the transcription of metallothionein proteins in two mural cell subsets and proinflammatory immune cells. Lastly, cellular communication analysis revealed that proinflammatory signaling, including TRAIL, PVR, CSF and GDF, were uniquely activated in patients with metabolic dysfunction. Conclusions: Our results identified critical cell-specific responses and cellular interactions in GSVs. Beyond serving as a repertoire, this work illustrates multifactorial likelihood of VGF.

Chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans (PGs) are major extracellular matrix (ECM) components of the central nervous system (CNS). A large body of evidence has shown that CSPGs/DSPGs play critical roles in neuronal growth, axon guidance, and plasticity in the developing and mature CNS. It has been proposed that these PGs exert their function through specific interaction of CS/DS chains with its binding partners in a manner that depends on the sulfation patterns of CS/DS. It has been reported that dermatan 4-O-sulfotransferase-1 (Chst14/D4st1) specific for DS, but not chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1) specific for CS, regulates proliferation and neurogenesis of neural stem cells (NSCs), indicating that CS and DS play distinct roles in the self-renewal and differentiation of NSCs. However, it remains unknown whether specific sulfation profiles of DS has any effect on CNS plasticity. In the present study, Chst14/D4st1-deficient (Chst14−/−) mice was employed to investigate the involvement of DS in synaptic plasticity. First, behavior study using Morris Water Maze (MWM) showed that the spatial learning and memory of Chst14−/− mice was impaired when compared to their wild type (WT) littermates. Corroborating the behavior result, long-term potentiation (LTP) at the hippocampal CA3-CA1 connection was reduced in Chst14−/− mice compared to the WT mice. Finally, the protein levels of N-Methyl-D-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, postsynaptic density 95 (PSD95), growth associated protein 43 (GAP-43), synaptophysin (SYN) and N-ethylmaleimide sensitive factor (NSF) which are important in synaptic plasticity were examined and Chst14/D4st1 deficiency was shown to significantly reduce the expression of these proteins in the hippocampus. Further studies revealed that Akt/mammalian target rapamycin (mTOR) pathway proteins, including protein kinase B (p-Akt), p-mTOR and p-S6, were significantly lower in Chst14−/− mice, which might contribute to the decreased protein expression. Together, this study reveals that specific sulfation of DS is critical in synaptic plasticity of the hippocampus and learning and memory, which might be associated with the changes in the expression of glutamate receptors and other synaptic proteins though Akt/mTOR pathway.

It has been reported that social isolation stress could be a key factor that leads to cognitive deficit for both humans and rodent models. However, detailed mechanisms are not yet clear. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We have hypothesized that social isolation stress may impact the expression of ADAR1 in the brain of mice with cognitive deficit. To test our hypothesis, we evaluated the cognition ability of mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expression in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress induced spatial and non-spatial cognition deficits of the tested mice. In addition, social isolation significantly increased both the immunoreactivity and protein expression of ADAR1 (p110) in the hippocampus and frontal cortex. Furthermore, re-socialization could not only recover the cognition deficits, but also bring ADAR1 (p110) immunoreactivity of hippocampus and frontal cortex, as well as ADAR1 (p110) protein expression of hippocampus back to the normal level for the isolated mice in adolescence. In conclusion, social isolation stress significantly increases ADAR1 (p110) expression in the hippocampus and frontal cortex of the mice with cognitive deficit. This finding may open a window to better understand the reasons (e.g., epigenetic change) that are responsible for social isolation-induced cognitive deficit and help the development of novel therapies for the resulted diseases.

Research on the acoustic performance of an anechoic coating composed of cavities in a viscoelastic material has recently become an area of great interest. Traditional forward research methods are unable to manipulate sound waves accurately and effectively, are difficult to analyse, have time-consuming solution processes, and have large optimization search spaces. To address these issues, this paper proposes a deep learning-based inverse research method to efficiently invert the material parameters of Alberich-type sound absorption coatings and rapidly predict their acoustic performance. First, an autoencoder (AE) model is pretrained to reconstruct the viscoelastic material parameters of an Alberich-type sound absorption coating, the material parameters are extracted into the latent feature space by the encoder, and the decoder model is saved. The internal relationship between the reflection coefficient and latent feature space is trained to establish a multilayer perceptron (MLP). Then, the reflection coefficients in the test set are input to the trained MLP and decoder models to automatically invert the material parameters. The accuracy of the inversion result is 95.08%. Finally, a predictive model is trained to rapidly predict the acoustic performance of the inverted material parameters. The speed of a single test target is 80 times faster than that of the finite element method (FEM). Furthermore, sound absorber material parameters with the best sound absorption performance and a three-band sound absorber are inverted, and their actual sound absorption performance is predicted by the proposed method. The proposed deep learning-based inversion research method provides a solution for low-frequency, wide-band, strong attenuation, and precisely controlled sound waves. It achieves an efficient inversion of material parameters and the rapid forecasting of acoustic performance. The training model can be used for a sound absorbing coating composed of irregular cavities in a viscoelastic material and predict its acoustic performance by only modifying the dataset. [ABSTRACT FROM AUTHOR]

A cavity viscoelastic structure has a good sound absorption performance and is often used as a reflective baffle or sound absorption cover in underwater acoustic structures. The acoustic performance field has become a key research direction worldwide. Because of the time-consuming shortcomings of the traditional numerical analysis method and the high cost of the experimental method for measuring the reflection coefficient to evaluate the acoustic performance of coatings, this innovative study predicted the reflection coefficient of a viscoelastic coating containing a cylindrical cavity based on an artificial neural network (ANN). First, themapping relationship between the input characteristics and reflection coefficient was analysed. When the elastic modulus and loss factor value were smaller, the characteristics of the reflection coefficient curve were more complicated. These key parameters affected the acoustic performance of the viscoelastic coating. Second, a dataset of the acoustic performance of the viscoelastic coating containing a cylindrical cavity was generated based on the finite elementmethod (FEM), which avoided a large number of repeated experiments. The minmax normalization method was used to preprocess the input characteristics of the viscoelastic coating, and the reflection coefficient was used as the dataset label. The grid search method was used to fine-tune the ANNparameters, and the prediction error was studied based on a 10-fold cross-validation. Finally, the error distributions were analysed. The average root means square error (RMSE) and the mean absolute percentage error (MAPE) predicted by the improved ANN model were 0.298% and 1.711%, respectively, and the Pearson correlation coefficient (PCC) was 0.995, indicating that the improved ANN model accurately predicted the acoustic performance of the viscoelastic coating containing a cylindrical cavity. In practical engineering applications, by expanding the database of the material range, cavity size and backing of the coating, the reflection coefficient of more sound-absorbing layers was evaluated, which is useful for efficiently predicting the acoustic performance of coatings in a specific frequency range and has great application value. [ABSTRACT FROM AUTHOR]

The impact of the presence of various [alpha] and [beta] chains of hemoglobin on the production of Staphylococcus aureus exotoxins is discussed. The findings reveal that these hemoglobin chains highly inhibit the production of Staphylococcus aureus strains.

The protective effects of dioscin, a natural steroidal saponin from some medicinal plants including Dioscorea nipponica Makino, against lipopolysaccharide (LPS)-induced acute liver and renal damages have been reported in our previous works. However, the actions of dioscin against LPS-induced acute lung injury (ALI) is still unknown. In the present study, we investigated the effects and mechanisms of dioscin against LPS-induced ALI in vitro and in vivo. The results showed that dioscin obviously inhibited cell proliferation and markedly decreased reactive oxidative species level in 16HBE cells treated by LPS. In addition, dioscin significantly protected LPS-induced histological changes, inhibited the infiltration of inflammatory cells, as well as decreased the levels of MDA, SOD, NO and iNOS in mice and rats (p < 0.05). Mechanistically, dioscin significantly decreased the protein levels of TLR4, MyD88, TRAF6, TKB1, TRAF3, phosphorylation levels of PI3K, Akt, IkBa, NF-kB, and the mRNA levels of IL-1β, IL-6, and TNF-α against oxidative stress and inflammation (p < 0.05). Dioscin significantly reduced the overexpression of TLR4, and obviously down-regulated the levels of MyD88, TRAF6, TKB1, TRAF3, p-PI3K, p-Akt, p-IkBα, and p-NF-kB. These findings provide new perspectives for the study of ALI. Dioscin has protective effects on LPS-induced ALI via adjusting TLR4/MyD88- mediated oxidative stress and inflammation, which should be a potent drug in the treatment of ALI. [ABSTRACT FROM AUTHOR]

Purpose: To study the reactivity of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) with the cationically charged agents cetylpyridinium chloride, stannous fluoride, and the non-cationic agent triclosan. We also assessed the effect of these agents to inhibit LPS and LTA binding to cellular Toll-like Receptors (TLRs) in vitro. Methods: The ability of these antimicrobials to bind with LPS and/or LTA was assessed in both the Limulus amebocyte lysate and BODIPY-TR-cadaverine dye assays. Mass spectroscopy was then used to confirm that stannous fluoride directly binds with LPS and to determine stoichiometry. Lastly, we looked for possible inhibitory effects of these antimicrobial agents on the ability of fluorescently conjugated LPS to bind to TLR4 expressed on HEK 293 cells. Results: Cetylpyridinium chloride (CPC) and stannous salts including stannous fluoride interfered with LPS and LTA reactivity in both dye assays, while triclosan had no effect. Mass spectroscopy revealed direct binding of stannous fluoride with E. Coli LPS at 1:1 stoichiometric ratios. In the cellular assay, cetylpyridinium chloride and stannous fluoride, but not triclosan, inhibited LPS binding to TLR4. [ABSTRACT FROM AUTHOR]

In search of new antileukopenia agents, twenty dithiolopyrrolone derivatives were synthesized and evaluated for their leukocyte-increasing activities in normal mice. Among the synthesized compounds 4-23, compounds 5 and 6 showed significant leukocyte-increasing activity ( p < 0.01), and compounds 4, 9 and 16 had a moderate effect ( p < 0.05). Compound 5 also displayed stronger leukocyte-increasing activity than that of the positive recombinant human granulocyte colony stimulating factor (rhG-CSF). Above all, compound 5 would be a potential antileukopenia agent which deserved further research. [ABSTRACT FROM AUTHOR]

Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably little is known at the molecular level. We describe the genome, secretory proteome, and expression of selected genes of Malassezia globosa. Further, we report a comparative survey of the genome and secretory proteome of Malassezia restricta, a close relative implicated in similar skin disorders. Adaptation to the skin environment and associated pathogenicity may be due to unique metabolic limitations and capabilities. For example, the lipid dependence of M. globosa can be explained by the apparent absence of a fatty acid synthase gene. The inability to synthesize fatty acids may be complemented by the presence of multiple secreted lipases to aid in harvesting host lipids. In addition, an abundance of genes encoding secreted hydrolases (e.g., lipases, phospholipases. aspartyl proteases, and acid sphingomyelinases) was found in the M. g!obosa genome. In contrast, the phylogenetically closely related plant pathogen Ustilago maydis encodes a different arsenal of extracellular hydrolases with more copies of glycosyl hydrolase genes. M. globosa shares a similar arsenal of extracellular hydrolases with the phylogenetically distant human pathogen, Candida albicans, which occupies a similar niche, indicating the importance of host-specific adaptation. The M. globosa genome sequence also revealed the presence of mating-type genes, providing an indication that Malassezia may be capable of sex. [ABSTRACT FROM AUTHOR]

We will show that ocean-reflected signals from the global positioning system (GPS) navigation satellite constellation can be detected from a low-earth orbiting satellite and that these signals show rough correlation with independent measurements of the sea winds. We will present waveforms of ocean-reflected GPS signals that have been detected using the experiment onboard the United Kingdom's Disaster Monitoring Constellation satellite and describe the processing methods used to obtain their delay and Doppler power distributions. The GPS bistatic radar experiment has made several raw data collections, and reflected GPS signals have been found on all attempts. The down linked data from an experiment has undergone extensive processing, and ocean-scattered signals have been mapped across a wide range of delay and Doppler space revealing characteristics which are known to be related to geophysical parameters such as surface roughness and wind speed. Here we will discuss the effects of integration time, reflection incidence angle and examine several delay-Doppler signal maps. The signals detected have been found to be in general agreement with an existing model (based on geometric optics) and with limited independent measurements of sea winds; a brief comparison is presented here. These results demonstrate that the concept of using bistatically reflected global navigation satellite systems signals from low earth orbit is a viable means of ocean remote sensing. [ABSTRACT FROM AUTHOR]

Examines the penicillin-binding protein 2a (PBP2a) from methicillin-resistant Staphylococcus aureus. Kinetic characteristics of PBP2a interactions with beta-lactams; PBP2a overexpression in Echerichia coli; Purification to homogeneity; Determination of covalent adducts formation by HPLC-electrospray mass spectrometry.

The article presents a study that explores how tumor suppressor CCAAT/enhancer binding protein-alpha (CEBPA) interacts with and inhibits DNA methyltransferases (DNMT3A) activity. It mentions about the DNA methyltransferases (DNMTs) catalyze DNA methylation, and their functions in mammalian embryonic development and diseases.

There is a need to investigate the role of nuclear factor kappa B in the regulation of cyclooxygenase-2 expression in the epileptic rat brain and cultured hippocampal neurons. Immunofluorescence and polymerase chain reaction was used to detect the expression of nuclear factor kappa B and cyclooxygenase-2. In cultured hippocampal neurons and rat brain: the control group compared with the normal group, nuclear factor kappa B expression in the hippocampal dentate gyrus, cerebral cortex, the piriform cortex brain regions were significantly increased (P < 0.01). This is accompanied by a significant increase in cyclooxygenase-2 protein and mRNA expressions in the hippocampus (P < 0.01). In the experimental group compared to the control group, the nuclear factor-kappa B expression in the hippocampal dentate gyrus, cerebral cortex, piriform cortex, and other brain regions was significantly lower (P < 0.01), with the accompanying decrease in cyclooxygenase-2 protein and mRNA expression (P < 0.01) in the hippocampus. In conclusion, κB-decoy can inhibit nuclear factor kappa B activation in epileptic rat brain and cyclooxygenase-2 overexpression.

The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Glyceraldehyde-3-phosphate dehydrogenase is a pivotal glycolytic enzyme and implicated in many human cancers. Results: GAPDH acetylation promotes its activity in response to glucose via the action of PCAF and HDAC5. Conclusion: GAPDH acetylation promotes cell proliferation and tumor growth. Significance: This study demonstrates a critical role of GAPDH acetylation in tumor growth and provides potential therapy target for cancer. [ABSTRACT FROM AUTHOR]

Dandruff and seborrheic dermatitis (D/SD) are common hyperproliferative scalp disorders with a similar etiology. Both result, in part, from metabolic activity of Malassezia globosa and Malassezia restricta, commensal basidiomycete yeasts commonly found on human scalps. Current hypotheses about the mechanism of D/SD include Malassezia-induced fatty acid metabolism, particularly lipase-mediated breakdown of sebaceous lipids and release of irritating free fatty acids. We report that lipase activity was detected in four species of Malassezia, including M. globosa. We isolated lipase activity by washing M. globosa cells. The isolated lipase was active against diolein, but not triolein. In contrast, intact cells showed lipase activity against both substrates, suggesting the presence of at least another lipase. The diglyceride-hydrolyzing lipase was purified from the extract, and much of its sequence was determined by peptide sequencing. The corresponding lipase gene (LIP1) was cloned and sequenced. Confirmation that LIP1 encoded a functional lipase was obtained using a covalent lipase inhibitor. LIP1 was differentially expressed in vitro. Expression was detected on three out of five human scalps, as indicated by reverse transcription-PCR. This is the first step in a molecular description of lipid metabolism on the scalp, ultimately leading toward a test of its role in D/SD etiology.Journal of Investigative Dermatology (2007) 127, 2138–2146; doi:10.1038/sj.jid.5700844; published online 26 April 2007 [ABSTRACT FROM AUTHOR]